Sofosbuvir Plus Ravidasvir for the Treatment of HCV Chronic Infection

Tracking Information
First Submitted Date ICMJE	September 7, 2016
First Posted Date ICMJE	November 11, 2016
Last Update Posted Date	May 11, 2017
Study Start Date ICMJE	September 2016
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 8, 2016)	Sustained Virological Response 12 weeks post treatment completion (SVR12), as evidenced by HCV RNA level less than the lower limit of quantification of 15 IU/mL [ Time Frame: Outcome measure of sustained virological response will be assessed 12 weeks after the end of the treatment (SVR 12) as soon as the data will be available ]; In case of positive HCV RNA, HCV sequences at base line and 12 weeks post treatment completion will be compared to rule out reinfection. Reinfections are not considered as failures
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT02961426 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Sofosbuvir Plus Ravidasvir for the Treatment of HCV Chronic Infection
Official Title ICMJE	Open Label Phase II/III, Multicenter, Trial to Assess the Efficacy, Safety, Tolerance, and Pharmacokinetics of Sofosbuvir Plus Ravidasvir in HCV (+/- HIV) Chronically Infected Adults With no or Compensated Cirrhosis in Thailand and Malaysia
Brief Summary	This is a Phase II/III, multicenter, multi-country, trial to assess the efficacy, safety, tolerance, and pharmacokinetics of sofosbuvir plus ravidasvir for the treatment of HCV infection.
Detailed Description	The study will assess the efficacy and safety of SOF-RDV across all genotypes, among non-cirrhotic and cirrhotic with CTP class A, interferon/ribavirin naïve or experienced, HCV mono-infected and HCV/HIV co-infected subjects. It will also study the pharmacokinetics of RDV and, in HCV/HIV co-infected subjects, possible drug-drug interactions with antiretrovirals. The treatment duration will be 12 weeks for subjects with no cirrhosis (Metavir F0 to F3) and 24 weeks for subjects with compensated cirrhosis (Metavir F4, CTP class A). After enrollment of the first 300 evaluable patients is complete, enrollment will pause while data is being accumulated and analyzed. After review of interim results by the independent Data and Safety Monitoring Board (DSMB), and by the study Steering Committee, enrollment will resume. Should modification of the study design be required upon interim analysis, decision will be taken by the study steering committee and the amended protocol or expanded protocol will be submitted to the Ethics Committee for approval.
Study Type ICMJE	Interventional
Study Phase	Phase 2; Phase 3
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Hepatitis C
Intervention ICMJE	Drug: sofosbuvir; combination sofosbuvir ravidasvir treatment for non cirrhotic and compensated cirrhotic patients; Other Name: ravidasvir
Study Arms	non cirrhotic patient 12 weeks sofosbuvir ravidasvir Intervention: Drug: sofosbuvir; compensated cirrhotic patient 24 weeks sofosbuvir ravidasvir Intervention: Drug: sofosbuvir
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: November 8, 2016)	750
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	December 2018
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Evidence of chronic HCV infection, defined as: Positive anti-HCV antibody or detectable HCV RNA or HCV genotype at least 6 months before screening and HCV viral load ≥104 IU/mL at the time of screening In subjects without documented HCV test results 6 months before screening, chronic hepatitis C infection can be assumed if risk exposures occurred > 6 months prior to screening and HCV viral load ≥104 IU/mL at the time of screening.; Willing and able to provide written informed consent.; Men and women age ≥ 18 years and < 70 years.; Body Mass Index (BMI) of 18 to 35 kg/m2.; Intention to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.; Women with a negative pregnancy test at screening and baseline.; Women of child bearing potential who accept effective contraception from 2 weeks prior to study day 1 until 1 month post-treatment (Double contraceptive method including at least one barrier method). A woman is of non-child bearing potential if she (a)reached natural menopause determined retrospectively after 12 months of amenorrhea without any other obvious medical cause or (b)had procedures like bilateral tubal ligation or hysterectomy or bilateral oophorectomy.; Subjects who are compliant in opioid substitution maintenance program may be included as long as there is no concern about study medications adherence and interaction or compliance to study schedules. Active illicit drug users may also be enrolled, as a pre-stratified subpopulation, however their data will not contribute in the primary intent to treat analysis Exclusion Criteria: Decompensated cirrhosis defined as: Evidence of advanced stage liver cirrhosis and Child-Turcotte-Pugh (CTP) Class B or C or CTP score >6) or current/past history of decompensation including ascites, variceal bleeding, spontaneous bacterial peritonitis, or hepatic encephalopathy.; Hepatocellular carcinoma; To exclude hepatocellular carcinoma (HCC), liver imaging within 6 months prior to screening is required for all subjects with cirrhosis and this must continue periodically as in routine HCC surveillance.; Additional laboratory exclusion criteria:; cirrhotic subjects with albumin < 2.8 g/dL; direct bilirubin > 3xULN; AST, ALT > 10xULN; Low neutrophil count (≤599 cells/mm3), hemoglobin (<9.0 g/dL for male, <8.5 g/dL for female), platelets (<50000 cells/mm3 ) classified as ≥ Grade 3; Patients with serum creatinine > 1.5 ULN or end stage renal disease; Hepatitis B co-infection (HBsAg positive); Pregnancy, as documented by positive pregnancy tests at screening and baseline; Breastfeeding; Subjects currently receiving or unable to stop the use for at least 1 week prior to receiving the first dose of study drug any medications or herbal supplements known to be potent inhibitors or moderate inducers of cytochrome P450 (CYP) 3A4 and potent inducers of P-glycoprotein. This includes subjects who are on amiodarone or other contraindicated drugs; Participation in other clinical trials within 3 months, except upon agreement with the study steering committee.; Any clinically significant findings or unstable condition during the screening, medical history or physical examination that, in the investigator's opinion, would compromise participation in this study . This could include patients with poorly controlled hypertension, asthma, diabetes, or other life-threatening conditions.; Current or history of use within the preceding 6 months of immunosuppressive or immune-modulating agents.; History of solid organ or bone marrow transplantation.; Any prior NS5A inhibitors therapy.; Patients with significant cardiovascular conditions including myocardial infarction within the previous 6 months or heart failure NYHA class III or IV; history of Torsade de pointes; QTcF value ≥ 450 milliseconds or third degree heart block;; Use of medications associated with QT prolongation concurrently or within the 30 days prior to Screening Visit, including: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, and tricyclic anti-depressants. Note: An electrocardiogram will be performed at screening and in case of doubt, the subject will be referred to a cardiologist for advice. Subjects will be instructed to immediately consult if they experience dizziness, light headedness or fainting spell. - HIV/HCV co-infected patients not yet on stable antiretroviral therapy or for whom ART treatment initiation maybe scheduled during the study period.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 70 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Lallemand Marc, MD +41 79 293 12 05 mlallemand@dndi.org Contact: francois simon +41791967868 fsimon@dndi.org
Listed Location Countries ICMJE	Malaysia, Thailand
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT02961426
Other Study ID Numbers ICMJE	DNDi-SOF/RDV-01-HCV
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Plan to Share IPD: Undecided
Responsible Party	Drugs for Neglected Diseases
Study Sponsor ICMJE	Drugs for Neglected Diseases
Collaborators ICMJE	Ministry of Health, Malaysia
Investigators ICMJE	Study Director: Lallemand Marc, MD Drugs for Neglected Diseases Principal Investigator: Soek-Siam Tan Selayang Hospital
PRS Account	Drugs for Neglected Diseases
Verification Date	May 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP